Non Inferiority Study of Preoperative Chemotherapy Without Pelvic Irradiation for Rectal Cancer

Prior treatment

• Prior pelvic irradiation or any contraindication to pelvic irradiation
• Contraindication to oxaliplatin or irinotecan or 5FU based chemotherapy
• Concomitant treatment with warfarin is contraindicated and warafarin must be replaced whenever possible to allow for inclusion.
• Recent or concomitant treatment with brivudine is contraindicated
• Concomitant treatment with millepertuis.
• live attenuated vaccine should not be used during and 6 months after preoperative treatment.
• Previous colorectal cancer

Other illness

• Metastatic disease
• contraindications to 5-FU: complete and permanent insufficiency in dihydropyrimidine dehydrogenase, bone marrow insufficiency, chronic and severe infection
• contraindications to folinic acid : Biermer anemia and other anemia related to B12 vitamin insufficiency
• Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Lab values

• contraindication to irinotecan : inflammatory bowel disease, bilirubin serum level \> 3 times the upper limit of the normal rate, severe bone marrow insufficiency, WHO/ECOG performence status \> 2,
• contraindication to oxaliplatin :
  • \*bone marrow insufficiency before treatment initiation (neutrophil count \<2x109/L and/or platelet count \<100x109/L), peripheral neuropathy with permanent invalidity before treatment initiation
• severe renal insufficiency (Creatinin clearance \<30 ml/min)
• contraindications to capecitabin : severe renal insufficiency (Creatinin clearance \<30 ml/min), complete and permanent insufficiency in dihydropyrimidine dehydrogenase

Age

• Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for \>5 years

Other

• Rectal tumor \> 10 cm from the anal verge on MRI (sagittal slide)
• cT4 tumor on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound) or involvement of external sphincter
• Circumferential margin ≤ 2 mm on pretreatment imaging work up (pelvic contrast enhanced MRI)
• protected adults
• Pregnancy or breastfeeding
• Patient with no national health or universal plan affiliation coverage.

• Histologically proven middle or low rectal carcinoma, ≤ 10 cm from the anal verge on MRI (sagittal slide)
• cT3N0 and/or cT1-T3N+ on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound),
• Pretreatment predictive circumferential margin \> 2mm on pretreatment imaging work up (pelvic contrast enhanced MRI)
• Patients must be 18 years old or older
• A World Health Organization (WHO/ECOG) performance status of 0 or 1
• Informed consent signed
• Patients of childbearing / reproductive potential should use adequate birth control measures during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.